Treatment of Endometrial Hyperplasias with Gonadotropin-Releasing Hormone Agonists: Pathological, Clinical, Morphometric, and DNA-Cytometric Data

Abstract

On the basis of the recently reported observation that gonadotropin-releasing hormone agonists (GnRH-a) can affect endometrial cell proliferation, both indirectly, through the hormonal axis, and directly, by acting on the GnRH-a receptors, we investigated how far GnRH-a can be used as a new treatment mode for endometrial hyperplasias. Forty-two women, aged 28–60 years, with histologically confirmed simple (n= 30) or complex (n= 12, 2 with atypias) hyperplasia of the endometrium were involved in the study. According to the protocol they were treated for 6 months with GnRH-a (leuprolide acetate or triptorelin), and each patient underwent uterine curettage in the third and the sixth month of treatment, and 6 and at least 12 months after cessation of the treatment, for histological examination and morphometric and DNA-cytometric evaluation of the endometrium (mean pathological follow-up, 19.2 months; mean clinical follow-up, 30.7 months). During treatment, most of the women first revealed endometrial atrophy, and, after cessation of the treatment, again an atrophic or mainly functional endometrium; in 7 women, all with initial diagnosis of simple hyperplasia, the endometrial hyperplasia reappeared, which led in all 7 cases to hysterectomy. The mean values of almost all morphometric and DNA-cytometric parameters during and after treatment showed statistically significant changes in relation to pretreatment values, indicating a decrease in the proliferative activity of the endometrial cells; the GnRH-a antiproliferative effect was still active for a long time after cessation of the therapy. Our results, based for the first time not only on histological but also on serial nuclear morphometric and DNA-cytometric examinations of the endometrial cells and on the longest follow-up time, support the view that in cases of endometrial hyperplasia, especially of complex type, the use of GnRH agonists, which decrease the proliferative tendency of endometrial cells, could represent an alternative conservative therapeutic approach, which, however, requires close monitoring of the endometrium.